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Irish Travellers constitute a pre-demographic-shift population living among a post-demographic-shift one. Their socio-medico profile identifies them as largely on fast life-history trajectories. In addition, they are strongly religious (typically using no contraception), highly sexually behaviorally dimorphic, with strong traditions of male-male competition (bare-knuckle fighting) and quasi-symbolic bride capture ("grabbing"). Their male-male competitions thus allow for the comparative testing of a number of interesting theories pertaining to the nature and function of types of violence in society. As a pilot study, we used expert raters (some naive to the hypotheses) to analyze a number of real-life bare-knuckle competitions in terms of the support said spectacles offered to theories of this sort of violence as reinforcing ideas of antisociality, hierarchical promotion, intersexual signaling, or maintenance of within-group equality. We found good evidence to support theories of within-group, prosocial hierarchical functions for these contests. Limitations and implications for future research, such as direct measurement of fitness, are discussed. [ABSTRACT FROM AUTHOR]

Understanding the role that therapists play in psychotherapy outcome, and the contribution to outcome made by individual therapist differences has implications for service delivery and training of therapists. In this study we used a novel approach to estimate the magnitude of the therapist contribution overall and the effect of individual therapist differences. We conducted a meta-analysis of studies in which participants were randomised to receive the same treatment either through self-help or through a therapist. We identified a total of 15 studies (commencement N = 910; completion N = 723) meeting inclusion criteria. We found no difference in treatment completion rate and broad equivalence of treatment outcomes for participants treated through self-help and participants treated through a therapist. Also, contrary to our expectations, we found that the variability of outcomes was broadly equivalent, suggesting that differences in efficacy of individual therapists were not sufficient to make therapy outcomes more variable when a therapist was involved. Overall, the findings suggest that self-help, with minimal therapist input, has considerable potential as a first-line intervention. The findings did not suggest that individual differences between therapists play a major role in psychotherapy outcome. [ABSTRACT FROM AUTHOR]

All humans must eventually face death at the end of life in this physical world. Nevertheless, sometimes sudden death can be horrendous, especially when associated with what appears to be unbearable pain during those final moments, such as being burned alive or beaten to death. The thought of a loved one having suffered such pain at the moment of death may intensify the degree of grief. However, despite the appearance of what sometimes appears to be conscious somatic suffering in those final moments, a non-pathological dissociation from that pain may have occurred. This paper explores this hypothesis, providing evidence of this occurring from research studies and/or self-reports. It then closes with a suggestion that knowledge of this phenomenon may provide some comfort to those in grief over a loved one who has undergone a horrible death in which extreme suffering seemed to have been present in those final moments. [ABSTRACT FROM AUTHOR]

The structures and energetics of centered 10-vertex Ge@Ge ( z = −4, −2, 0, +2, +4) clusters have been investigated by density functional theory (DFT) for comparison with the previously studied isomeric empty 11-vertex Ge clusters. For the cationic species ( z = +2, +4) such centered Ge@Ge structures are shown to be energetically competitive (within ∼1 kcal mol) to the lowest energy isomeric empty Ge structures. These Ge@Ge structures can be derived from the lowest energy empty 10-vertex Ge structures by inserting a Ge ion in the center. The outer 10-vertex polyhedron in the lowest energy Ge@Ge dication structure is the most spherical D bicapped square antiprism, which is also the lowest energy structure of the empty Ge dianion, as expected from the Wade-Mingos skeletal electron counting rules. For the tetracationic Ge/Ge@Ge system the lowest energy centered Ge@Ge structure can be obtained by inserting a Ge ion in the center of a C deltahedral empty Ge cluster. Centered 10-vertex polyhedral Ge@Ge structures were also found for the neutral ( z = 0) and dianionic ( z = −2) systems but at significantly higher energies than the lowest energy isomeric empty Ge structures. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Building on previous work that identified different types of orgasm in women (King, Belsky, Mah, & Binik, ), the goal of the present study was to extend such typological work and determine whether female orgasmic variability tracked potentially evolutionarily salient sexual partner characteristics (e.g., those displaying possible immune-system compatibility). A total of 265 females completed an Internet survey about their orgasmic experience-achieved either with partners or alone. For partnered orgasms, they also provided details of partner characteristics and sexual behaviors. Latent class analysis revealed two orgasm types which were meaningfully distinguishable in terms of sensations and location-either centered on the surface of genitalia or deep inside. Deep orgasms were associated with internal sensations consistent with proposed functions of female orgasm in terms of differential sperm insuck. Such orgasms were associated with partners who were perceived as considerate, dominant, with a noticeably attractive smell, and as providing firm penetration. However, some hypothesized reproductively significant partner characteristics were not differentially associated with deep orgasms (i.e., muscularity, aggression, masculinity). Results were discussed and future research directions outlined. In particular, it is suggested that sexual passion between partners is a non-accidental component of sexual functioning and that this has too frequently been missing in sex research involving humans. Direct physiological measures of the results of female orgasm need to be undertaken. Additionally, the intriguing phenomenon of female ejaculation deserves scientific attention. [ABSTRACT FROM AUTHOR]

In attempt to identify and validate different types of orgasms which females have during sex with a partner, data collected by Mah and Binik () on the dimensional phenomenology of female orgasm were subjected to a typological analysis. A total of 503 women provided adjectival descriptions of orgasms experienced either with a partner ( n = 276) or while alone ( n = 227). Latent-class analysis revealed four orgasm types which varied systematically in terms of pleasure and sensations engendered. Two types, collectively labelled 'good-sex orgasms,' received higher pleasure and sensation ratings than solitary-masturbatory ones, whereas two other types, collectively labelled 'not-as-good-sex orgasms,' received lower ratings. These two higher-order groupings differed on a number of psychological, physical and relationship factors examined for purposes of validating the typology. Evolutionary thinking regarding the function of female orgasm informed discussion of the findings. Future research directions were outlined, especially the need to examine whether the same individual experiences different types of orgasms with partners with different characteristics, as evolutionary theorizing predicts should be the case. [ABSTRACT FROM AUTHOR]

Natural and artificially created light fields in three-dimensional space contain lines of zero intensity, known as optical vortices. Here, we describe a scheme to create optical beams with isolated optical vortex loops in the forms of knots and links using algebraic topology. The required complex fields with fibred knots and links are constructed from abstract functions with braided zeros and the knot function is then embedded in a propagating light beam. We apply a numerical optimization algorithm to increase the contrast in light intensity, enabling us to observe several optical vortex knots. These knotted nodal lines, as singularities of the wave’s phase, determine the topology of the wave field in space, and should have analogues in other three-dimensional wave systems such as superfluids and Bose–Einstein condensates. [ABSTRACT FROM AUTHOR]

The Integrated Task Modeling Environment (ITME) is a user-friendly software tool that has been developed to automatically recode low-level data into an empirical record of meaningful task performance. The present research investigated and validated the performance of the ITME software package by conducting complex simulation missions and comparing the task analyses produced by ITME with task analyses produced by experienced video analysts. A very high interrater reliability (≥0.94) existed between experienced video analysts and the ITME for the task analyses produced for each mission. The mean session time:analysis time ratio was 1:24 using video analysis techniques and 1:5 using the ITME. It was concluded that the ITME produced task analyses that were as reliable as those produced by experienced video analysts, and significantly reduced the time cost associated with these analyses. [ABSTRACT FROM AUTHOR]

The article discusses various aspects of attention deficit hyperactivity disorder (ADHD) including the diagnosis and treatment among ethnic minority children. Ethnic minority children lack far behind in the rate of treatment and diagnosis of the disorder when compared to non-ethnic children. The ADHD Help-Seeking Behavior Model intends to facilitate the understanding of the factors, which may be predictive to service use.

Background: This study investigated the extent to which occupational therapists and social workers employed in Australian mental health settings are affected by burnout.Method: Questionnaires were sent to occupational therapists and social workers who had indicated that they were interested in participating in the study. An overall response rate of 76.6% (n = 304) was achieved. The outcome measure was the Maslach Burnout Inventory (comprising emotional exhaustion, depersonalisation and personal accomplishment scales).Results: There were no significant differences, with respect to any of the three burnout scales, between occupational therapists and social workers. Both groups experienced high emotional exhaustion, moderate depersonalisation, and high personal accomplishment. Levels of burnout were not significantly different between inpatient and community staff.Conclusions: These results suggested that, while occupational therapists and social workers reported emotional exhaustion, there was less evidence of depersonalisation and they reported very high personal accomplishment in their work. Results are congruent with those of previous studies and it is argued that the focus of future research should be on identifying characteristics of mental health work that contribute to emotional exhaustion. [ABSTRACT FROM AUTHOR]

This article examines the changes in the climate of thinking about treason and traitors since the end of World War II. If it can be said without tedious qualification and fear of misunderstanding that treason is an interesting topic and the traitor an interesting figure, sometimes even a sympathetic figure, no such inhibitions apply to the spy. The traitor-as-antihero is a romantic illusion that withers under close examination; there is nothing heroic about most spies and most traitors. What these men did sent innocent men to their deaths; good people were tortured and killed because of the things that Harold Philby, a counterespionage official of the British Military Intelligence, did. He betrayed Soviet defectors and guerillas in Eastern Europe who had aided England during World War II.

This article analyzes the connection between U.S. and British intellectuals, friendship, courage and treason. Treason has become somehow forgivable under a wider set of circumstances. Among some intellectuals the climate of thinking about treason and traitors has changed dramatically since the end of World War II, particularly since the end of the 1960s. There is no denying that the fascination of treason represents an object of intellectual inquiry and contemplation. This article will also explore the depiction of the issue of traitors and treason in the novels of E. M. Forster.

This study investigated the relationship between two therapist attributes (reflective functioning and attachment style) and client outcome. Twenty-five therapists treated a total of 1001 clients. Therapists were assessed for reflective functioning and attachment style using the Adult Attachment Interview and the Experiences in Close Relationships Scale. Clinical outcome was measured using the Outcome Questionnaire (OQ-45). Data were analysed using hierarchical linear modelling. Results indicated that therapist reflective functioning predicted therapist effectiveness, whereas attachment style did not. However, there was evidence of an interaction between therapist attachment style and therapist reflective functioning. Secure attachment compensated somewhat for low reflective functioning and high reflective functioning compensated for insecure attachment. Possible implications for the selection of therapy training candidates and therapist training are discussed. [ABSTRACT FROM AUTHOR]

Although trust is long known to be critical to predict behaviors in a charitable context, little research has examined trust damage and its effects on giving behavior. Trust damage is an intermediate state between trust and distrust, rather than a simple reversal or extension, and can change over time. Our research explores individual donor's trust damage through a dynamic evolution. Across the longitudinal survey, we conclude that the trust damage of pre-giving, giving, and post-giving stage plays different roles in the decision-making process. Trust damage does not play a direct role in the giving intention, but it can indirectly affect giving intention through its impact on perceived benefit and perceived risk. Individual donor's satisfaction has a strong effect on post-giving trust or continual trust damage, which in turn positively affects future giving intention and behavior. Several important insights for practitioners in the nonprofit sector are also discussed. [ABSTRACT FROM AUTHOR]

The article offers the author's insight on a case study questioning the duty of care of therapists to the client, their duty or obligation to the community, and their duty to themselves. He notes the duty of therapists in providing treatment within the scope of their practice. However, he observes that treatment in the case has contrary effect on the therapist's emotional well-being. He notices that the therapist is at risk of burnout which impairs her capacity to work effectively.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genomics Research on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of novel therapies. Here, we describe the objectives and methods of the TIC Genetics study as a reference for future studies from our group and to facilitate collaboration between genetics consortia in the field of TS. [ABSTRACT FROM AUTHOR]

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies. [ABSTRACT FROM AUTHOR]

Purpose: Limb immobilization causes local vasculature to experience detrimental adaptations. Simple strategies to increase blood flow (heating, fidgeting) successfully prevent acute (≤ 1 day) impairments; however, none have leveraged the hyperemic response over prolonged periods (weeks) mirroring injury rehabilitation. Throughout a 14-day unilateral limb immobilization, we sought to preserve vascular structure and responsiveness by repeatedly activating a reactive hyperemic response via blood flow restriction (BFR) and amplifying this stimulus by combining BFR with electric muscle stimulation (EMS). Methods: Young healthy adults (M:F = 14:17, age = 22.4 ± 3.7 years) were randomly assigned to control, BFR, or BFR + EMS groups. BFR and BFR + EMS groups were treated for 30 min twice daily (3 × 10 min ischemia–reperfusion cycles; 15% maximal voluntary contraction EMS), 5 days/week (20 total sessions). Before and after immobilization, artery diameter, flow-mediated dilation (FMD) and blood flow measures were collected in the superficial femoral artery (SFA). Results: Following immobilization, there was less retrograde blood velocity (+ 1.8 ± 3.6 cm s−1, P = 0.01), but not retrograde shear (P = 0.097). All groups displayed reduced baseline and peak SFA diameter following immobilization (− 0.46 ± 0.41 mm and − 0.43 ± 0.39 mm, P < 0.01); however, there were no differences by group or across time for FMD (% diameter change, shear-corrected, or allometrically scaled) nor microvascular function assessed by peak flow capacity. Conclusion: Following immobilization, our results reveal (1) neither BFR nor BFR + EMS mitigate artery structure impairments, (2) intervention-induced shear stress did not affect vascular function assessed by FMD, and (3) retrograde blood velocity is reduced at rest offering potential insight to mechanisms of flow regulation. In conclusion, BFR appears insufficient as a treatment strategy for preventing macrovascular dysfunction during limb immobilization. [ABSTRACT FROM AUTHOR]

Investigates the discrepancy of geodetically measured and geologically estimated convergence rates in the Ventura basin region of southern California. Possible implications; Presentation of constraints; Suggestion that the faults bounding the basin are locked in surface but slipping at depths.

Sustained silencing of gene expression throughout the brain using small interfering RNAs (siRNAs) has not been achieved. Here we describe an siRNA architecture, divalent siRNA (di-siRNA), that supports potent, sustained gene silencing in the central nervous system (CNS) of mice and nonhuman primates following a single injection into the cerebrospinal fluid. Di-siRNAs are composed of two fully chemically modified, phosphorothioate-containing siRNAs connected by a linker. In mice, di-siRNAs induced the potent silencing of huntingtin, the causative gene in Huntington's disease, reducing messenger RNA and protein throughout the brain. Silencing persisted for at least 6 months, with the degree of gene silencing correlating to levels of guide strand tissue accumulation. In cynomolgus macaques, a bolus injection of di-siRNA showed substantial distribution and robust silencing throughout the brain and spinal cord without detectable toxicity and with minimal off-target effects. This siRNA design may enable RNA interference-based gene silencing in the CNS for the treatment of neurological disorders. A divalent siRNA architecture enables sustained silencing of gene expression in deep regions of the brain. [ABSTRACT FROM AUTHOR]

Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and underlying pathophysiology with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of DSM-5 HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met DSM-5 criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive-compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models. [ABSTRACT FROM AUTHOR]

For select total knee arthroplasty (TKA) patients, we have established an alternative pathway to bypass the acute care surgical ward and directly admit patients from the post-anesthesia care unit to on-campus rehabilitation. We retrospectively examined whether this 'fast track' pathway decreased costs and improved patient outcomes. After reviewing records of consecutive primary unilateral TKA patients over a 15-month period, each patient admitted to rehabilitation was matched with a control admitted to the acute care ward. The primary outcome was estimated total hospitalization cost (length of stay in days multiplied by the average cost per day). Secondary outcomes were length of stay, in-hospital pain scores, opioid use, maximum ambulatory distance and 30-day readmission, morbidity, and mortality. Of the 262 TKA patients during the study period, 14 were admitted to rehabilitation and were matched to 14 patients admitted to acute care. Estimated total hospitalization cost [median (10th-90th percentiles)] was US$30,755 (US$23,066-38,444) for ward patients compared to US$17,620 (US$13,215-33,918) for rehabilitation patients ( P = 0.006). This difference [mean (95% CI)] was US$10,143 (US$2174-18,112). There were no other differences. For facilities similar to ours, direct postoperative admission of select TKA patients to subacute rehabilitation may be less costly than acute care and may not negatively affect outcomes. [ABSTRACT FROM AUTHOR]

The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N=1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P=0.014, OR=6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders. [ABSTRACT FROM AUTHOR]

Chronic tic disorders (TD) are consistently found to have high rates of comorbidity with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). The purpose of this study is to compare the severity of TD only to TD with comorbid OCD or ADHD based on severity of tics, measures of psychopathology and additional comorbid diagnoses. Baseline data from 158 youth with a chronic TD who participated in two longitudinal studies were examined. Fifty-three percent ( N = 85) of the youth also met criteria for a diagnosis of OCD, 38.6 % ( n = 61) met criteria for ADHD and 24.1 % ( N = 38) met criteria for both. Measures of interest addressed severity of tics, symptoms of anxiety, depression, ADHD, psychosocial stress, global functioning and the presence of comorbid diagnoses. Youth with comorbid TD and OCD were characterized by more severe tics, increased levels of depressive and anxious symptoms, heightened psychosocial stress and poorer global functioning. Youth with comorbid TD and ADHD did not differ from those with TD alone on measures of tic severity, but experienced greater psychosocial stress and poorer global functioning. Subjects with comorbid TD and OCD had more internalizing disorders than those without OCD, while those with comorbid ADHD were more likely to meet criteria for oppositional defiant disorder. TD with OCD is a more severe subtype of TD than TD without OCD. TD with ADHD is associated with higher psychosocial stress and more externalizing behaviors. Further research is needed into the underlying relationships between these closely associated conditions. [ABSTRACT FROM AUTHOR]

Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5 mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5 mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo ( p < 0.01). Although we found no overall reduction of the risk for PBH in treated patients, there may be an effect of low-dose BHT-3009, depending on the patients' pre-treatment immune responses. [ABSTRACT FROM AUTHOR]

ention-deficit/hyperactivity disorder (ADHD) is frequently diagnosed in children with Tourette syndrome (TS). The basis for this co-occurrence is uncertain. This study aimed to determine if specific pre- and perinatal risk factors, including heavy maternal smoking and severe psychosocial stress during pregnancy, were associated with one or both disorders, or neither. We compared maternal report data on pre- and perinatal risk factors on 222 children between the ages of 7 and 18 years including 45 individuals with TS alone, 52 individuals with ADHD alone, 60 individuals with condition of comorbid TS + ADHD, and 65 unaffected control children. Pre- and perinatal histories as well as psychiatric assessments were performed using standardized questionnaires and semi-structured interviews with the mothers and children. Logistic regression was used to determine the odds ratio for each variable of interest. Compared to the mothers of unaffected control children, the mothers of children with ADHD alone reported higher rates of heavy smoking (>10 cigarettes per day) during pregnancy and higher levels of severe psychosocial stress during pregnancy (OR = 13.5, p < 0.01 and OR = 6.8, p < 0.002, respectively). The TS + ADHD and the TS alone patients also had higher rates heavy maternal smoking and high levels of psychosocial stress compared to the control children, but these differences failed to reach statistical significance (heavy smoking: OR = 8.5, p < 0.052, OR = 4.6, p < 0.19, respectively; severe psychosocial stress: OR = 3.1, p < 0.07, OR = 2.6, p < 0.11, respectively). Heavy maternal smoking and severe levels psychosocial stress during pregnancy were independently associated with a diagnosis of ADHD. TS patients also had higher rates of these risk factors, but the ORs failed to reach statistical significance. Efforts are needed to reduce the frequency of these risk factors in high-risk populations. Future studies, using genetically sensitive designs, are also needed to sort out the causal pathways. [ABSTRACT FROM AUTHOR]

Advanced intercross lines (AIL) and interval–specific congenic strains (ISCS) were used to fine map previously coarsely defined quantitative trait loci (QTL) on Chromosomes 1,10, and 19, influencing behaviors in the open Field (OF) and light–dark (LD) paradigms in mice. F12(A × B) AIL mice ( N = 1130) were phenotyped, genotyped, and mapped. The ISCS were studied only in the telomeric Chromosome 10 region of interest, containing the exploratory and excitability QTL1 ( Exq1). The Chromosome 10 Exq1 and Chromosome 19 Exq4 loci mapped robustly in the AIL. The most significant QTL findings (2.0 LOD score intervals; peak; LOD score) came from the TD15 and LD transitions traits, yielding estimated intervals of 2.2 cM for Exq1 (71.3–73.5 cM; peak 72.3 cM; LOD 11.9) and 9.0 cM for Exq4 (29.0–38.2 cM; peak 34 cM; LOD 4.2). The replicated QTLs on Chromosome 1 failed to map in this AIL population. The ISCS data confirmed Exq1 loci in general. However, the ISCS data were complex and less definitive for localizing the Exq1 loci. These exploratory and fear-like behaviors result from inheriting “many small things,” namely, QTL explaining 2%–7% of the phenotypic variance. These results highlight the challenges of positionally cloning loci of small effect for complex traits. In particular, fine-mapping success may depend on the genetic architecture underlying complex traits. [ABSTRACT FROM AUTHOR]